全文获取类型
收费全文 | 1094篇 |
免费 | 78篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 43篇 |
妇产科学 | 57篇 |
基础医学 | 118篇 |
口腔科学 | 28篇 |
临床医学 | 141篇 |
内科学 | 266篇 |
皮肤病学 | 34篇 |
神经病学 | 20篇 |
特种医学 | 126篇 |
外科学 | 48篇 |
综合类 | 24篇 |
预防医学 | 56篇 |
眼科学 | 4篇 |
药学 | 50篇 |
1篇 | |
中国医学 | 3篇 |
肿瘤学 | 155篇 |
出版年
2023年 | 4篇 |
2021年 | 15篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 18篇 |
2017年 | 6篇 |
2016年 | 9篇 |
2015年 | 16篇 |
2014年 | 22篇 |
2013年 | 34篇 |
2012年 | 24篇 |
2011年 | 35篇 |
2010年 | 51篇 |
2009年 | 51篇 |
2008年 | 37篇 |
2007年 | 48篇 |
2006年 | 40篇 |
2005年 | 46篇 |
2004年 | 36篇 |
2003年 | 22篇 |
2002年 | 21篇 |
2001年 | 23篇 |
2000年 | 26篇 |
1999年 | 34篇 |
1998年 | 44篇 |
1997年 | 54篇 |
1996年 | 48篇 |
1995年 | 26篇 |
1994年 | 33篇 |
1993年 | 27篇 |
1992年 | 32篇 |
1991年 | 21篇 |
1990年 | 28篇 |
1989年 | 33篇 |
1988年 | 24篇 |
1987年 | 17篇 |
1986年 | 22篇 |
1985年 | 16篇 |
1984年 | 22篇 |
1983年 | 16篇 |
1982年 | 18篇 |
1981年 | 15篇 |
1980年 | 10篇 |
1979年 | 3篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 4篇 |
排序方式: 共有1177条查询结果,搜索用时 15 毫秒
31.
32.
Els M J J Berns Jan G M Klijn Maxime P Look Nicolai Grebenchtchikov Rolf Vossen Harry Peters Anneke Geurts-Moespot Henk Portengen Iris L van Staveren Marion E Meijer-van Gelder Bert Bakker Fred C G J Sweep John A Foekens 《Clinical cancer research》2003,9(4):1253-1258
PURPOSE: In recent studies, we showed that TP53 gene mutation or high levels of cytosolic vascular endothelial growth factor (VEGF) in estrogen receptor (ER)-alpha-positive primary breast tumors predict a poor disease outcome for patients treated with first-line tamoxifen for advanced disease. Mutant TP53 may up-regulate VEGF, whereas, on the other hand, wild-type TP53 may decrease VEGF production. EXPERIMENTAL DESIGN: In the present study, we aimed to assess the combined predictive value of TP53 gene mutation and VEGF status of 160 advanced breast cancer patients with ER-positive tumors who were treated with tamoxifen (median follow-up from start of tamoxifen treatment, 64 months). To assess TP53 gene mutation status, the entire open reading frame was sequenced; for VEGF status, an ELISA was used. RESULTS: In univariate analysis, both TP53 gene mutation (28% of the tumors) and a VEGF level above the median value were significantly associated with a short progression-free survival, post-relapse overall survival, and a poor rate of response to tamoxifen. In Cox multivariate regression analysis including the traditional predictive factors, the addition of TP53 gene mutation and VEGF status, alone or in combination, significantly predicted a poor efficacy of tamoxifen treatment. When the two factors were combined, a significantly decreased odds ratio was seen for the rate of response (odds ratio, 0.27). Similarly, an increased hazard ratio (HR) was seen for progression-free survival (HR, 2.32) and post-relapse overall survival (HR, 1.68) in the group with mutant TP53 and high VEGF compared with the group with both risk factors absent. CONCLUSIONS: Combined TP53 gene mutation status and high VEGF levels of ER-positive primary breast tumors independently predict a poor course of the disease of patients with advanced breast cancer treated with tamoxifen. These patients, having unfavorable tumor characteristics, might benefit more from other types of (individualized) treatment protocols. 相似文献
33.
OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation. 相似文献
34.
Iron-overload diseases frequently develop hepatocellular carcinoma. The
genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might
involve an oxidative process via the intermediate production of reactive
oxygen species. This was presently investigated by examining kinetics of
formation and repair of DNA base lesions in primary rat hepatocyte cultures
supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and
100 microM). Seven DNA base oxidation products have been identified in DNA
extracts by gas chromatography- mass spectrometry, which showed a
predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine,
2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil,
5-OH-cytosine) in control cultures. All these DNA oxidation products
revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA
supplementation, among which fapy-adenine showed the highest increase and
5-OH-cytosine was the least prominent. Involvement of iron in this
oxidative process was established by a correlation between extent in DNA
oxidation and intracellular level of toxic low molecular weight iron. DNA
excision- repair activity was estimated by release of DNA oxidation
products in culture medium. All the seven DNA oxidation products were
detected in the medium of control cultures and showed basal repair
activity. This DNA repair activity was increased in a time- and
dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was
5-OHMe-Uracil, were preferentially repaired, which explains the low levels
detected in oxidized DNA. Since oxidized bases substantially differed from
one another in terms of excision rates from cellular DNA, specific
excision- repair enzymes might be involved. Our findings, however,
demonstrate that even though DNA repair pathways were activated in
iron-loaded hepatocyte cultures, these processes were not stimulated enough
to prevent an accumulation of highly mutagenic DNA oxidative products in
genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in
understanding the hepatocarcinogenic evolution of iron-overload diseases.
相似文献
35.
36.
37.
Yuli R Tak Rinka MP Van Zundert Rowella CWM Kuijpers Boukje S Van Vlokhoven Hettie FW Rensink Rutger CME Engels 《BMC public health》2012,12(1):21
Background
The incidence of depressive symptoms increases during adolescence, from 10.0% to 24.5% at age 11 to 15, respectively. Experiencing elevated levels of depressive symptoms increases the risk of a depressive disorder in adulthood. A universal school-based depression prevention program Op Volle Kracht (OVK) was developed, based on the Penn Resiliency Program, aimed at preventing the increase of depressive symptoms during adolescence and enhancing positive development. In this study the effectiveness of OVK will be tested and possible mediators of program effects will be focus of study as well. 相似文献38.
39.
Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study 总被引:3,自引:0,他引:3
We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation. 相似文献
40.
Davis MA Landesman R Tadmor B Hopmeier M Shenhar G Barker T Pozner CN Binstadt ES Nelson S Look R Shubina M Walls RM 《Annals of emergency medicine》2008,51(4):420-5, 425.e1-5